Case Report of One Family With Coffin-Lowry Syndrome and Literature Review of 28 Cases in China

ZHU Diling, YANG Wenxu, ZHANG Lan

Abstract

Objective 

 To investigate the clinical phenotypes and genotypic characteristics of Chinese patients with Coffin-Lowry syndrome.

Methods 

 The clinical data and genetic test results of a family with Coffin-Lowry syndrome were retrospectively analyzed. A literature review was conducted to summarize the clinical characteristics and gene mutation characteristics of patients with Coffin-Lowry syndrome in China.

Results 

 The proband was a 1-year-old boy with distinctive facial features, puffy but tapered fingers, hypotonia, growth retardation, and delayed cognitive and motor development. Genetic analysis revealed a hemizygous c.1603-2A>G mutation in intron 17 of the RPS6KA3 gene in the proband. His mother was a heterozygous carrier. The identified mutation has not been reported previously. The proband′s maternal half-brother and half-sister also exhibited similar clinical manifestations and were diagnosed with Coffin–Lowry syndrome together with the proband. The proband was followed up until 3 years and 8 months old, by which time he was not capable of walking steadily independently or speech. Including the 4 members of this family, a total of 28 Chinese patients were identified. Their clinical manifestations included special facial features (100%), cognitive and language/motor developmental delays (92.6%), hypotonia (95.2%), tapered fingers (88.5%), and scoliosis or kyphosis (45%). Genetic sequencing was performed in 24 patients, revealing missense mutations in 3 cases (12.5%), frameshift mutations in 5 cases (20.8%), nonsense mutations in 9 cases (37.5%), splice-site mutations in 4 cases (16.7%), and exon deletions in 2 cases (8.3%). No mutation hotspots were identified.

Conclusion 

Coffin-Lowry syndrome should be considered in children with cognitive and language/motor developmental delays, distinctive facial features, tapered fingers, and hypotonia. Genetic testing can assist with early diagnosis.

 

Keywords: Coffin-Lowry syndrome, RPS6KA3 gene, High-throughput sequencing

 

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References


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